The principal objective of this study is to establish graded dose-response data for several known and quantifiable effects of narcotics in rats in the presence and absence of narcotic antagonists. Investigations will be conducted in both naive and dependent animals. Although emphasis is placed on morphine, other narcotics will also be used. From among the effects in the spectrum of opiate actions, four endpoints will be measured: seizure threshold, pupillary effects, analgesia and heat production. The influence of brain lesions and alterations in socioenvironmental conditions on the narcotic actions will also be investigated. All studies will be carried out in conjunction with an assessment of the significance of local concentrations of the drugs. By using modern receptor theory, the data can aid in determining whether or not the several effects are mediated through a single receptor or through several central and peripheral receptors. The information to be gained is useful both as a supplement to that derived from tissue binding studies as well as for its own sake in classifying central drug receptors. These studies will allow for a rational estimate of the possibility of separating unwanted side effects from the desirable actions of these drugs. Finally, studies of interactions between morphine and other drugs of abuse will aid in approaching the problem of treatment of multiple drug abusers.